Relationship of MMP-14 and TIMP-3 Expression with Macrophage Activation and Human Atherosclerotic Plaque Vulnerability
Joint Authors
Johnson, Jason L.
Jenkins, Nicholas P.
Huang, Wei-Chun
Di Gregoli, Karina
Sala-Newby, Graciela B.
Scholtes, Vincent P. W.
Moll, Frans L.
Newby, Andrew C.
Pasterkamp, Gerard
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-08-21
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Matrix metalloproteinase-14 (MMP-14) promotes vulnerable plaque morphology in mice, whereas tissue inhibitor of metalloproteinases-3 (TIMP-3) overexpression is protective.
MMP-14 hi TIMP-3 lo rabbit foam cells are more invasive and more prone to apoptosis than MMP-14 lo TIMP-3 hi cells.
We investigated the implications of these findings for human atherosclerosis.
In vitro generated macrophages and foam-cell macrophages, together with atherosclerotic plaques characterised as unstable or stable, were examined for expression of MMP-14, TIMP-3, and inflammatory markers.
Proinflammatory stimuli increased MMP-14 and decreased TIMP-3 mRNA and protein expression in human macrophages.
However, conversion to foam-cells with oxidized LDL increased MMP-14 and decreased TIMP-3 protein, independently of inflammatory mediators and partly through posttranscriptional mechanisms.
Within atherosclerotic plaques, MMP-14 was prominent in foam-cells with either pro- or anti-inflammatory macrophage markers, whereas TIMP-3 was present in less foamy macrophages and colocalised with CD206.
MMP-14 positive macrophages were more abundant whereas TIMP-3 positive macrophages were less abundant in plaques histologically designated as rupture prone.
We conclude that foam-cells characterised by high MMP-14 and low TIMP-3 expression are prevalent in rupture-prone atherosclerotic plaques, independent of pro- or anti-inflammatory activation.
Therefore reducing MMP-14 activity and increasing that of TIMP-3 could be valid therapeutic approaches to reduce plaque rupture and myocardial infarction.
American Psychological Association (APA)
Johnson, Jason L.& Jenkins, Nicholas P.& Huang, Wei-Chun& Di Gregoli, Karina& Sala-Newby, Graciela B.& Scholtes, Vincent P. W.…[et al.]. 2014. Relationship of MMP-14 and TIMP-3 Expression with Macrophage Activation and Human Atherosclerotic Plaque Vulnerability. Mediators of Inflammation،Vol. 2014, no. 2014, pp.1-17.
https://search.emarefa.net/detail/BIM-1043461
Modern Language Association (MLA)
Johnson, Jason L.…[et al.]. Relationship of MMP-14 and TIMP-3 Expression with Macrophage Activation and Human Atherosclerotic Plaque Vulnerability. Mediators of Inflammation No. 2014 (2014), pp.1-17.
https://search.emarefa.net/detail/BIM-1043461
American Medical Association (AMA)
Johnson, Jason L.& Jenkins, Nicholas P.& Huang, Wei-Chun& Di Gregoli, Karina& Sala-Newby, Graciela B.& Scholtes, Vincent P. W.…[et al.]. Relationship of MMP-14 and TIMP-3 Expression with Macrophage Activation and Human Atherosclerotic Plaque Vulnerability. Mediators of Inflammation. 2014. Vol. 2014, no. 2014, pp.1-17.
https://search.emarefa.net/detail/BIM-1043461
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1043461